A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

Gao, Feng; Huang, Jingjing; Li, Tingting; Hu, Chao; Shen, Meiying; Mu, Song; Luo, Feiyang; Song, Shuyi; Hao, Yanan; Wang, Wang; Han, Xiaojian; Chen, Qian; Wang, Ying‐Ming; Wu, Ruixue; Luo, Li; Li, Shenglong; Jin, Aishun

doi:10.3389/fimmu.2021.789905

Cited by 14 publications

(8 citation statements)

References 35 publications

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“…In this study, mice immunized with oEV-S1 via mucosal routes (oral and IN) also exhibited an increased number of splenic plasma cells in comparison to mice treated with oEV vehicle alone. A similar result was also reported by Gao et al [ 61 ] as an increase in the ratio of CD19−CD138+ plasma cells in total lymphocytes derived from the spleen of mice immunized with RBD9.1 peptide.…”

Section: Discussionsupporting

confidence: 89%

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pomatto

Gai

Negro³

et al. 2023

Pharmaceutics

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Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (Citrus sinensis) juice (oEVs) were investigated as carriers for oral and intranasal SARS-CoV-2 mRNA vaccine. oEVs were efficiently loaded with different mRNA molecules (coding N, subunit 1 and full S proteins) and the mRNA was protected from degrading stress (including RNase and simulated gastric fluid), delivered to target cells and translated into protein. APC cells stimulated with oEVs loaded with mRNAs induced T lymphocyte activation in vitro. The immunization of mice with oEVs loaded with S1 mRNA via different routes of administration including intramuscular, oral and intranasal stimulated a humoral immune response with production of specific IgM and IgG blocking antibodies and a T cell immune response, as suggested by IFN-γ production by spleen lymphocytes stimulated with S peptide. Oral and intranasal administration also triggered the production of specific IgA, the mucosal barrier in the adaptive immune response. In conclusion, plant-derived EVs represent a useful platform for mRNA-based vaccines administered not only parentally but also orally and intranasally.

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Section: Discussionsupporting

confidence: 89%

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pomatto

Gai

Negro³

et al. 2023

Pharmaceutics

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“…Vaccination with the entire Spike protein possessing mutated RBD, however, would not efficiently induce mutated RBD-specific Abs, as most of these Spike protein-specific Abs would be unable to detect the few mutated amino acids of RBD [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The development of vaccines that generate Abs able to neutralize hACE2-mediated infection requires a consideration of the domain antigen of RBD and the defined epitope antigen [ 15 , 16 , 17 , 18 , 19 ]. Clinical trials have reported that several RBD-containing vaccines could induce nAbs and protect against SARS-CoV-2 infection with acceptable adverse events [ 10 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

et al. 2023

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SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We identified closed linear epitopes of the SARS-CoV-2 Spike molecule that induced neutralizing Abs (nAbs) against both S1-RBD, responsible for attachment to hACE2, and S2-HR1/2, in convalescents and vaccine recipients. They inhibited a pseudo-virus infection mediated by the hACE2 pathway. The epitope sequences included epitopes #7 (aa411-432), #11 (aa459-480) and #111 (aa1144-1161), in S1-RBD and S2-HR2. Epitope #111 was conserved in Wuhan and variant strains, whereas #7 and #11 were conserved in Wuhan carried mutations K417N and S477N/T478K in Omicron BA.4/5. These mutations were recognized by the original epitope-specific Abs. These epitopes in RBD and HR2 neither contained, nor overlapped with, those responsible for the antibody-dependent enhancement of the SARS-CoV-2 infection. The sublingual administration of multiple epitope-conjugated antigens increased the IgG and IgA Abs specific to the neutralizing epitopes in mice pre-immunized subcutaneously. The findings indicated that S1-RBD and S2-HR2 epitopes were responsible for pseudo-virus SARS-CoV-2 infections and that sublingual boosts with multiple epitope-conjugated antigens could enhance the protection by nAbs of IgG and IgA against infection by a wide range of variants.

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“…58G6 and 55A8 were 2 NAbs identified from patients convalescing from COVID-19 in early 2019 ( 31 , 38 – 40 ). 55A8 could bind to the spike (S) proteins of WT SARS-CoV-2 and its mutational variants, including Delta and Omicron BA.1, BA.2, and BA.5, as tested by enzyme-linked immunosorbent assay (ELISA) ( Supplemental Figure 1 , A and B; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.171034DS1 ).…”

Section: Resultsmentioning

confidence: 99%

Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron

Zhang,

Luo,

Zhang

et al. 2024

JCI Insight

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BACKGROUND As Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need. METHODS The applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity. RESULTS The 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay. CONCLUSION These results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections. TRIAL REGISTRATION www.chictr.org.cn, ChiCTR2200066525. FUNDING The National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

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A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

Cited by 14 publications

References 35 publications

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron

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